The periodontal tissue which is composed of gingiva, alveolar bone, periodontal ligament (periodontal membrane), cementum, dental pulp, etc. is essential for erecting teeth and maintaining their functions such as mastication and occlusion, and its damage or destruction will lead to the loss of teeth. Consider, for example, a periodontal disease which is reportedly afflicting about 30 million people in Japan; as the disease progresses, the periodontal tissue becomes increasingly damaged or destroyed resulting in tooth loss. To treat damaged or destroyed periodontal tissue including the dental pulp, various methods comprising medication and surgical operation are being attempted but none of the medicaments and therapeutic methods are sufficiently effective to regenerate the damaged or destroyed periodontal tissue including the dental pulp.
Neurotrophic factors include brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5) and are involved in differentiation, survival, regeneration and functional maintenance of neuron. BDNF and NT-4/5 bind to the high-affinity receptor TrkB (tropomyosin receptor kinase B), NGF to TrkA, and NT-3 to TrkC.
BDNF, NGF and NT-3 are neurotrophic factors mostly present in the brain and the efficacy of BDNF and NGF has been demonstrated in experiments with animals of various disease models such as a motor neuropathy model, a Parkinson's disease model, and an Alzheimer disease model. In particular, BDNF is expected as an effective therapeutic drug for motor and peripheral nervous diseases such as amyotrophic lateral sclerosis (ALS) and peripheral neuropathies due to diabetes and chemotherapeutic agents, and for diseases involving the central nervous system such as the Alzheimer disease, the Parkinson's disease, and retina-related diseases.
These neurotrophic factors are said to play an important role not only in the central nervous system but also in the peripheral nervous system. It has been reported that the expression of BDNF, NGF, NT-3, TrkC and TrkA increased during the healing process of fractured mouse ribs (K. Asaumi et al., Bone, Vol. 26, No. 6, 625-633, 2000) and that BDNF, NGF and NT-3 enhanced the proliferation of mouse periodontal ligament cells (Y. Tsuboi et al., J Dent Res 80(3):881-886, 2001). However, there are no detailed reports on the behavior of those neurotrophic factors in the periodontal tissue and pulp tissue.